Articular cartilage chondrocyte metabolism is inhibited in a dose-dependent and apparent irreversible manner by selected prostaglandins (PG), and exposure to rheumatoid synovial secretions. The variable in vitro response is attributed to differential tissue sensitivity, tissue preparation techniques and inconsistent purity of PG preparations. De novo synthesis of PG by chondrocytes is altered following exposure to exogenous PG presumably mediated by accelerated release of arachidonic acid. This positive feedback system and irreversible inhibition of cartilage may have significant bearing on the chronicity of articular cartilage destruction following episodic or transitory inflammation.